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@ARTICLE{Brocka:139981,
      author       = {Brocka, Marta and Helbing, Cornelia and Vincenz, Daniel and
                      Scherf, Thomas and Montag, Dirk and Goldschmidt, Jürgen and
                      Angenstein, Frank and Lippert, Michael},
      title        = {{C}ontributions of dopaminergic and non-dopaminergic
                      neurons to {VTA}-stimulation induced neurovascular responses
                      in brain reward circuits.},
      journal      = {NeuroImage},
      volume       = {177},
      issn         = {1053-8119},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {DZNE-2020-06303},
      pages        = {88-97},
      year         = {2018},
      abstract     = {Mapping the activity of the human mesolimbic dopamine
                      system by BOLD-fMRI is a tempting approach to non-invasively
                      study the action of the brain reward system during different
                      experimental conditions. However, the contribution of
                      dopamine release to the BOLD signal is disputed. To assign
                      the actual contribution of dopaminergic and non-dopaminergic
                      VTA neurons to the formation of BOLD responses in target
                      regions of the mesolimbic system, we used two optogenetic
                      approaches in rats. We either activated VTA dopaminergic
                      neurons selectively, or dopaminergic and mainly
                      glutamatergic projecting neurons together. We further used
                      electrical stimulation to non-selectively activate neurons
                      in the VTA. All three stimulation conditions effectively
                      activated the mesolimbic dopaminergic system and triggered
                      dopamine releases into the NAcc as measured by in vivo
                      fast-scan cyclic voltammetry. Furthermore, both optogenetic
                      stimulation paradigms led to indistinguishable
                      self-stimulation behavior. In contrast to these
                      similarities, however, the BOLD response pattern differed
                      greatly between groups. In general, BOLD responses were
                      weaker and sparser with increasing stimulation specificity
                      for dopaminergic neurons. In addition, repetitive
                      stimulation of the VTA caused a progressive decoupling of
                      dopamine release and BOLD signal strength, and dopamine
                      receptor antagonists were unable to block the BOLD signal
                      elicited by VTA stimulation. To exclude that the sedation
                      during fMRI is the cause of minimal mesolimbic BOLD in
                      response to specific dopaminergic stimulation, we repeated
                      our experiments using CBF SPECT in awake animals. Again, we
                      found activations only for less-specific stimulation. Based
                      on these results we conclude that canonical BOLD responses
                      in the reward system represent mainly the activity of
                      non-dopaminergic neurons. Thus, the minor effects of
                      projecting dopaminergic neurons are concealed by
                      non-dopaminergic activity, a finding which highlights the
                      importance of a careful interpretation of reward-related
                      human fMRI data.},
      keywords     = {Animals / Behavior, Animal: physiology / Brain: diagnostic
                      imaging / Brain: metabolism / Brain: physiology / Dopamine:
                      metabolism / Dopamine Antagonists: pharmacology /
                      Dopaminergic Neurons: physiology / Electric Stimulation /
                      Electrodes, Implanted / Genetic Vectors / Magnetic Resonance
                      Imaging: methods / Neurons: metabolism / Neurons: physiology
                      / Neurovascular Coupling: physiology / Optogenetics / Rats /
                      Rats, Long-Evans / Rats, Transgenic / Rats, Wistar / Reward
                      / Self Stimulation: physiology / Stereotaxic Techniques /
                      Tomography, Emission-Computed, Single-Photon / Ventral
                      Tegmental Area: diagnostic imaging / Ventral Tegmental Area:
                      metabolism / Ventral Tegmental Area: physiology / Dopamine
                      Antagonists (NLM Chemicals) / Dopamine (NLM Chemicals)},
      cin          = {AG Angenstein},
      ddc          = {610},
      cid          = {I:(DE-2719)1310004},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29723641},
      doi          = {10.1016/j.neuroimage.2018.04.059},
      url          = {https://pub.dzne.de/record/139981},
}